Field of the Invention
The invention relates to a composition comprising at least one injectable corticosteroid and a diluent, preferable an anesthetic solution, which is suitable for producing medicaments to diminish small fat accumulations on the face and body by causing atrophy of the fat cells.
Description of Related Art
At present, subcutaneous accumulations of fat are treated by surgical procedures through liposuction or direct surgical removal. For small fat deposits, such those occurring with aging in some areas of the face, liposuction is too aggressive and is associated with the known complications or risks.
Injectable drugs, such as phosphatidylcholine (PPC) and sodium deoxycholate, also known as lipodissolve agents, were also used in some years ago (particularly in Brazil up to 2002), although there are no studies proving their safety and efficacy. Moreover, these drugs were also associated with severe side effects, including death in animals. (Paschoal L H, Lourenço L, Ribeiro A, et al. Um alerta! Efeitos sistêmicos e teciduais da fosfatidilcolina em suínos [poster]. Presented at 16° Congresso Brasileiro de Cirurgia Dermatológica. Porto de Galinhas June, 2004).
US2005/0143347 describes a method for removing subcutaneous accumulation of fat as well as aqueous preparations comprising at least one phospholipid and/or at least one bile acid and a component assisting degradation of fat such as riboflavin. Since the bile acids cause important inflammation where they are injected, an anti-inflammatory compound can be added in the preparation.
The term “corticosteroids” means compounds from the adrenal cortex. In technical terms, corticosteroid refers to both glucocorticoids and mineralocorticoids (as both are mimics of hormones produced by the adrenal cortex), but is often used as a synonym for glucocorticoid. Glucocorticoids are a class of steroid hormones characterized by an ability to bind with the glucocorticoid receptor (GR) and trigger similar effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by their specific receptors, target cells, and effects.
Glucocorticoids have potent anti-inflammatory and immunosuppressive properties. This is particularly evident when they are administered at pharmacologic doses, but also is important in normal immune responses. As a consequence, glucocorticoids are indicated for the treatment of many different conditions, including allergies, autoimmune diseases and inflammatory disease like asthma (New England J Med 2005; 353:1711-23).
Corticosteroids can be used topically, orally and by injections. Injectable corticosteroids currently used in medicine include the short-Acting injectable corticosteroids such as cortisone and hydrocortisone; the intermediate-Acting Injectable corticosteroids such as Prednisone, Prednisolone tebutate, Triamcinolone and Methylprednisolone its derivatives such as methylprednisolone acetate; the long-Acting corticosteroids such as Dexamethasone and its derivatives such as Dexamethasone sodium phosphate and Betamethasone its derivatives such as betamethasone dipropionate, betamethasone disodium phosphate and betamethasone acetate, and others.
Triamcinolone and other systemic corticosteroids have strong anti-inflammatory effects and this explains the large use of these compounds in medicine. At Medline, more than twenty-five thousands papers are published on injectable corticosteroids and more than five thousands papers on triamcinolone are published. Injectable corticosteroids are usually commercialized in stable aqueous suspension and are also described in the patent applications or patents such as U.S. Pat. No. 6,395,294 owned by Triesence (exploitation by Alcon) until Jan. 13, 2020 for Triamcinolone acetonide in intravitreal injectable form.
Triamcinolone acetonide injectable suspension USP (Kenalog®-40 Injection, Bristol-Myers Squibb Company, Italy) is a synthetic corticosteroid designed to provide systemic immunosuppressant and anti-inflammatory effects, as well as other intralesional or sublesional local effects for various skin diseases and conditions. The drug is stable at room temperature and must be shaken well before using.
Triamcinolone and/or other injectable corticosteroids are commonly used in dermatology for intralesional injections, as well as in other specialties and diseases, such as for joint inflammation and pain. Intralesional corticosteroids injections release a high concentration of the drug directly on the action site, with minimal systemic absorption. These drugs are considered very safe, low cost and efficient for an expressive number of diseases and conditions, for patients of different ages. Few applications and low doses are considered extremely safe, also for patients presenting severe diseases.
The aging process is caused by intrinsic and extrinsic aging, as well as changes in hard and soft tissues. Muscular hyperactivity causes dynamic wrinkles, currently treated by botulinum toxins. The losses in hard and soft tissues are currently being treated by fillers. The surface alterations are being treated by ablative and non-ablative techniques, as well as by topical retinoids and other active ingredients. There are no currently medical approved drugs for age-related fat accumulations on the face and beyond, except deoxicholate for submental fat. It was also reported that fat pads like those occurring under the eyes, on the abdomen or on the hips can be treated by phosphatidylcholine and people who received subcutaneous injection of Lipostabil® N I.V. showed esthetic improvements in their appearance. (Patricia Guedes Rittes, The Use of Phosphatidylcholine for Correction of Lower Lid Bulging Due to Prominent Fat Pads, Dermatol. Surg. 2001; 27: 391-392). Residual small fat deposits are also common complaints after liposuction.
Thus, the term “age related fat deposits” of the face are the ones to be treated according to the present invention. These fat accumulations were located in the face as following: under the eyes, pre-jowl fat and submental fat.
However, a new compound approved in the US use the deoxycholate, marketed as Kibella® by Allergan. US2005/0261258 proposes compositions and methods useful in the non-surgical removal of localized fat deposits in patients in need thereof using pharmacologically active detergents are disclosed. The deposit is contacted with a composition consisting essentially of an effective amount of up to 5% deoxycholic acid or salt thereof and an excipient wherein said deoxycholic acid or salt thereof is a sole fat removing component. Even if efficient, this product is known as being painful during the injection. There is a need to find a new product that could be efficient in reducing the fat without cause any kinds of discomfort or pain in the patient. Furthermore, it is important to mention that Kibella is not recommended for age related fat deposits, but for (exclusively) submental fat.